The innate cellular immune response in bacterial urinary tract infection

Abstract

Urinary tract infections (UTI), such as cystitis or pyelonephritis, affect a large proportion of the world population and most of these infections are caused by UPEC bearing distinct virulence factors. Immune mediators established to be of importance for innate immune defense against UPEC include antimicrobial substances such as reactive oxygen species, exfoliation of uroepithelial cells and infiltration of neutrophil granulocytes (NΦG). In many infections, also macrophages (MΦ) and dendritic cells (DC) have been shown to be recruited by various chemokine receptors to sites of infection. Recruitment and functional role of these cells in UTI, however, are unknown. We found that DC and two subsets of MΦ, CX3CR1-expressing Gr1^LO MФ and CCR2 expressing Gr1HI MФ, were infiltrating the bladder after infection. These subsets have been described in other infections, but it remained unresolved whether they exerted distinct immune effector functions. In UTI, only Gr1LO MФ produced iNOS, whereas Gr1^HI MФ effectively produced TNFα. All phagocytes examined produced ß1 defensin-1 and not only epithelial cells as previously proposed. Interestingly, NΦG were most active at phagocytosis of UPEC. These findings are the first to reveal functional differences between Gr1^LO and Gr1^HI MФ in infection. <br /> Moreover, the factors responsible for egress and immigration of MФ in UTI were identified using a recently described <i>in vivo</i> labeling technique. Finally, CCR2 contributed to the abundance of monocytes in the blood and the bladder and may affected the release of monocytes from the bone marrow (BM) into the circulation.<br /> In conclusion, the present study revealed mechanisms important in recruitment, migration and for expression of effector functions by different phagocyte cell types against bacterial infections. These findings advance our understanding of immunity against bacterial infections and extended the molecular mechanism important for egress and immigration of monocytes throughout the organism.